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N J Vogelzang

Publications and source records attributed to N J Vogelzang.

At least 19 recordsLinked to original sources
PubMed2005

A phase I study of antisense oligonucleotide GTI-2040 given by continuous intravenous infusion in patients with advanced solid tumors.

BACKGROUND: This study of GTI-2040, a 20-mer phosphorothioate oligonucleotide complementary to the messenger ribonucleic acid (mRNA) of the R2 subunit of ribonucleotide reductase (RNR), was conducted to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of the agent in patients with advanced solid tumors or lymphoma. Plasma pharmacokinetics of GTI-2040 and suppression of RNR expression in peripheral blood mononuclear cells were also studied. PATIENTS AND METHODS: GTI-2040 was administered as a continuous intravenous infusion for 21 days every 4 weeks. Dose escalation was performed using an accelerated, dose-doubling schedule until any drug related toxicity > or = grade 2 was observed; subsequent dose escalation followed a more conservative dose escalation scheme with three patients/cohort. RESULTS: A total of 49 cycles of therapy were administered to 36 patients at GTI-2040 doses ranging from 18.5 mg/m(2)/day to 222 mg/m(2)/day. GTI-2040 was generally well tolerated. At the highest dose level examined, two patients experienced dose limiting reversible hepatic toxicity. Constitutional toxicities consisting of fatigue and anorexia were the most common toxicities. CONCLUSIONS: The recommended dose of GTI-2040 given on this infusion schedule is 185 mg/m(2)/day. GTI-2040 appears to have a manageable toxicity profile and is generally well tolerated as a single agent.

Adult↗
PubMed2005

Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma.

BACKGROUND: A phase III trial in patients with malignant pleural mesothelioma demonstrated a survival advantage for pemetrexed plus cisplatin compared with single-agent cisplatin. Because post-study chemotherapy (PSC) may have influenced the outcome of the trial, we examined its use and association with survival. PATIENTS AND METHODS: Eighty-four patients from the pemetrexed plus cisplatin arm and 105 patients from the single-agent cisplatin arm received PSC. Kaplan-Meier survival estimates were compared by treatment groups, and by PSC and non-PSC subgroups. RESULTS: The percentage of patients receiving PSC was imbalanced between the treatment arms. Fewer pemetrexed plus cisplatin treated patients received PSC (37.2% versus 47.3%). A multiple regression analysis performed in this trial showed that PSC had a statistically significant correlation with prolonged survival (P <0.01), adjusting for baseline prognostic factors and treatment intervention. The adjusted hazard ratio for PSC over non-PSC subgroups was 0.56 (confidence interval 0.44-0.72). CONCLUSIONS: PSC in malignant pleural mesothelioma was significantly associated with prolonged survival. It is not known whether the reduced risk of death was associated with PSC or whether patients who had prolonged survival tended to receive more PSC. The pemetrexed plus cisplatin treatment group had a statistically significant survival advantage even though fewer patients from that arm of the trial received PSC. The potentially beneficial role of PSC should be assessed in prospective trials.

Adult↗
PubMed2005

Long-term follow-up of nonmyeloablative allogeneic stem cell transplantation for renal cell carcinoma: The University of Chicago Experience.

Nonmyeloablative allogeneic stem cell transplantation (NST) has considerable activity in patients with metastatic renal cell carcinoma (RCC), although there are limited long-term follow-up data. Between February 1999 and May 2003, 18 patients with metastatic RCC underwent 19 matched-sibling NSTs after conditioning with fludarabine and cyclophosphamide with tacrolimus and mycophenolate mofetil as post-transplant immunosuppression. Among the four objective responses, all were partial and have relapsed with a median response duration of 609 days (range, 107-926). All responders are alive at a median of 41 months. Median overall survival for the entire cohort was 14 months. There were four early treatment-related deaths and one late treatment-related death. Eight patients died from progressive disease and five (28%) from treatment-related mortality. Stratifying transplant outcome as early death, intermediate (no response, no early death), or response, the combination of pre-treatment anemia and decreased performance status, was associated with adverse outcome (P = 0.015) and reduced survival (HR 5.4, 95% confidence interval of 1.4 to 21, P = 0.007). Responders demonstrated prolonged survival compared to nonresponders (P = 0.002). NST leads to durable responses in a minority of metastatic RCC patients. Appropriate patient selection is paramount. Anemia and decreased performance status may enable risk stratification.

Adult↗
PubMed2004

Clinical responses following nonmyeloablative allogeneic stem cell transplantation for renal cell carcinoma are associated with expansion of CD8+ IFN-gamma-producing T cells.

Nonmyeloablative allogeneic stem cell transplantation (NST) is thought to be an immunologic therapy in which donor T cells mediate a graft-versus-tumor effect. We recently reported the clinical outcome of a phase II trial of NST in metastatic renal cell carcinoma (RCC). However, the immune response correlates of clinical activity remain unknown. We now describe the analysis of T-cell subsets and T-cell cytokine-producing potential for those patients evaluable for immune monitoring. The incidence of graft-versus-host disease (GVHD) correlated with clinical outcome, with all responders exhibiting chronic GVHD. Following initial tapering of immunosuppression, an increase in the total numbers of CD8+ T cells but not CD4+ T cells was observed among responders compared to nonresponders. In addition, a greater ratio of CD8+ to CD4+ T cells producing IFN-gamma and IL-2 was seen in clinical responders at the time when clinical responses were first detected (day 180 after transplantation). Our results support the hypothesis that the antitumor effects of NST may be mediated by IFN-gamma-producing CD8+ T cells, and indicate that isolation of putative tumor antigen-specific T cells, ideally, should be pursued around day +180.

Adult↗
PubMed2004

Depletion of normal B cells with rituximab as an adjunct to IL-2 therapy for renal cell carcinoma and melanoma.

BACKGROUND: We postulated that in patients with metastatic renal cell carcinoma (RCC) or melanoma, depletion of normal B cells using the anti-CD20 mAb rituximab before treatment with low-dose interleukin (IL)-2 would improve clinical outcome. PATIENTS AND METHODS: Rituximab (375 mg/m(2)) weekly for 4 weeks. IL-2 [11 (million units) daily] s.c., 4 days a week for weeks 5-8, followed by a 2-week rest (weeks 9 and 10). Patients without disease progression continued on IL-2. Disease re-evaluation was performed after rituximab and after every course of IL-2. RESULTS: Fifteen patients with RCC and six with melanoma were enrolled. One patient had a partial response and seven patients had stable disease. Toxicities were similar to those expected with IL-2 alone, and there were no grade 4 events. Circulating B cells were depleted in all patients. The subsequent low-dose IL-2 increased absolute numbers of natural killer cells, activated CD4(+) and activated CD8(+) T cells. Expanded T cells produced interferon-gamma, but not IL-4. Proliferation of peripheral blood lymphocytes to phytohemagglutinin was diminished following rituximab treatment, suggesting that B cells participate in this response in vitro. CONCLUSIONS: Our results suggest that depletion of circulating B cells with rituximab does not increase the response rate, alter the toxicity profile or change the biological activity in response to low-dose IL-2 in patients with RCC or melanoma.

Adult↗
PubMed2004

A phase I study of the oral combination of CI-994, a putative histone deacetylase inhibitor, and capecitabine.

BACKGROUND: This study was conducted to determine the toxicity profile, maximum tolerated dose (MTD) and pharmacokinetics of the putative histone deacetylase inhibitor CI-994 in combination with capecitabine. PATIENTS AND METHODS: Fifty-four patients were treated according to three different dosing schemes in which the capecitabine dose was fixed and the CI-994 dose was escalated. Capecitabine was administered in twice daily divided doses, and CI-994 was given as a single daily dose. In schedule A, 26 patients were treated with capecitabine 1650 mg/m2/day and CI-994 for 2 weeks of a 3-week cycle. In schedule B, six patients received capecitabine 1650 mg/m2/day for two 3-week cycles and CI-994 for 5 of 6 weeks. In schedule C, 22 patients were treated with capecitabine 2000 mg/m2/day and CI-994 for 2 of 3 weeks. RESULTS: At the MTD, the principal dose-limiting toxicity was thrombocytopenia. The pharmacokinetics of CI-994 were unaltered by capecitabine, and there was no correlation between body surface area and major pharmacokinetic parameters. Platelet count nadir was best predicted by the observed maximal concentration (C(max)) of CI-994. CONCLUSIONS: The recommended phase II dose is 6 mg/m2 (or 10 mg) of CI-994 in combination with capecitabine 2000 mg/m2/day for 2 weeks of a 3-week cycle.

Administration, Oral↗
PubMed2003

Phase I and pharmacokinetic study of 24-hour infusion 5-fluorouracil and leucovorin in patients with organ dysfunction.

BACKGROUND: Patients with hepatic or renal dysfunction are often treated with 5-fluorouracil (5-FU), but there are few data to confirm the safety of this practice. PATIENTS AND METHODS: Patients with solid tumors were eligible if they were able to fit into one of three organ dysfunction cohorts: I, creatinine >1.5 but < or =3.0 mg/dl and normal bilirubin; II, bilirubin >1.5 but <5.0 mg/dl with normal creatinine; or III, bilirubin > or =5.0 mg/dl with normal creatinine. 5-FU doses were escalated separately within each of the three cohorts. Leucovorin (LV) dosage was fixed at 500 mg/m(2). 5-FU was given as a 24-h infusion at 1000, 1800 or 2600 mg/m(2), and plasma concentrations were measured every 3 h during the first two infusions for each patient. RESULTS: Sixty-four patients were treated. Toxicities did not appear to be related to organ dysfunction cohort. A weekly dose of of 5-FU 2600 mg/m(2) produced dose-limiting toxicity (DLT) in six of 20 evaluable patients. These DLTs included grade 3 fatigue (n = 3), grade 2 neutropenia precluding weekly dosing (n = 1), grade 3 thrombocytopenia (n = 1) and grade 3 mental status changes (n = 1). There was no relationship between serum bilirubin or serum creatinine and 5-FU clearance. CONCLUSIONS: Patients with elevated bilirubin may be safely started on a weekly regimen of 5-FU 2600 mg/m(2) with leucovorin 500 mg/m(2) as a 24-h continuous infusion.

Adult↗
PubMed2002

A phase II trial of oral temozolomide in patients with metastatic renal cell cancer.

PURPOSE: To determine the activity of temozolomide, an oral imidazotetrazine alkylating agent that has exhibited broad antitumor activity in preclinical studies, in renal cell cancer (RCC) patients. METHODS. Metastatic RCC patients were treated with temozolomide, 200 mg/m(2) per day orally, and traditional radiologic response endpoints were assessed. O(6)-Alkylguanine-DNA alkyltransferase (AGT) activity was measured in four pretreatment biopsies. RESULTS: Among 12 patients, there were no responses. High AGT activity was observed in all four biopsies analyzed. CONCLUSIONS: Temozolomide is not active against RCC and this clinical observation may be due to high levels of AGT in this tumor.

Aged↗
PubMed2002

A phase II trial of weekly intravenous gemcitabine and cisplatin with continuous infusion fluorouracil in patients with metastatic renal cell carcinoma.

BACKGROUND: We reported previously that the combination of gemcitabine and continuous infusion fluorouracil (5-FU) has activity in renal cell carcinoma. Based upon in vitro synergy of gemcitabine/cisplatin and 5-FU/cisplatin, we hypothesized that the addition of cisplatin could improve the objective response rate of gemcitabine and 5-FU with manageable toxicity. PATIENTS AND METHODS: Twenty-one patients with metastatic renal cell carcinoma (RCC) and a Cancer and Leukemia Group B performance status of 0 to 2 were enrolled. Ten had received prior systemic therapy. Treatment consisted of gemcitabine 600 mg/m2 and cisplatin 20 mg/m2 on days 1, 8 and 15 of each 28-day cycle. Continuous infusion 5-FU was given from day 1 to day 21. RESULTS: No complete responses and one partial response were observed for an objective response rate of 5% (95% confidence interval 0% to 24%). Two minor responses (25% to 50% regression) were also observed. The median overall survival was 10 months with 35% of patients surviving at 1 year. Grade 3-4 myelosuppression (mostly thrombocytopenia) occurred in nine (43%) patients. Nausea/vomiting and neuropathy were dose-limiting in an additional five patients. Only 51% of treatment cycles were delivered on time and without dose reduction. CONCLUSIONS: The addition of cisplatin to gemcitabine and 5-FU did not improve the objective response rate of gemcitabine and 5-FU alone and added to the toxicity. Due to the cumulative toxicity, further trials with this cisplatin-containing regimen in RCC are not indicated.

Adult↗
PubMed2001

Phase I study to evaluate multiple regimens of intravenous 5-fluorouracil administered in combination with weekly gemcitabine in patients with advanced solid tumors: a potential broadly active regimen for advanced solid tumor malignancies.

BACKGROUND: The purpose of this study was to determine the maximum tolerated dose and toxicity profile of gemcitabine given on a weekly schedule with continuous infusion 5-fluorouracil. PATIENTS AND METHODS: Eligible patients with advanced solid tumors received escalating doses of gemcitabine 200 and 300 mg/m(2) weekly as a 30-minute infusion on Days 1, 8, and 15 every 4 weeks (schedule 1) or 450, 600, 800, 1000, 1250, 1500, 1800, and 2200 mg/m(2) on Days 1 and 8 (schedule 2) every 3 weeks, respectively. At the completion of gemcitabine infusion (Day 1), patients received fixed dose continuous infusion of 5-fluorouracil at either 300 mg/m(2) (Days 1-21) or 200 mg/m(2) (Days 1-21; schedule 1) every 4 weeks or 200 mg/m(2) (Days 1-14; schedule 2] every 3 weeks, respectively. Toxicity assessments were performed weekly on study, and efficacy measurements were performed every 6-8 weeks. RESULTS: Seventy patients with advanced solid malignancies received a total of 220 cycles of combination chemotherapy. Eleven (14.3%) patients received no more than 1 treatment cycle of combination therapy. Schedule 1 maximum tolerated dose of gemcitabine was 600 mg/m(2)/week when combined with 5-fluorouracil (5-FU) at 200 mg/m(2)/day (Days 1-21) repeated every 4 weeks. The schedule 2 maximum tolerated dose of gemcitabine was 2200 mg/m(2)/week when combined with 5-FU dosed at 200 mg/m(2)/day (Days 1-14) repeated every 3 weeks. In schedule 1, the limiting factor for gemcitabine delivery was the Day 15 dose that often was omitted because of myelosuppression and/or mucositis. In schedule 1 cycle 1, nonhematologic toxicity was common and included Grade 3-4 toxicities: mucositis (8 patients), fatigue (2 patients), and anorexia (1 patient). One patient had Grade 3-4 neutropenia at dose level 5 (maximum tolerated dose). In schedule 2 cycle 1, hematologic toxicities were more common than nonhematologic toxicity and included Grade 3 anemia (3 patients), Grade 3 neutropenia (4 patients), and Grade 3 thrombocytopenia (2 patients). The nonhematologic toxicities included Grade 3 mucositis (3 patients), Grade 3 fatigue (2 patients), and Grade 3 dehydration (1 patient). Overall, antitumor activity was observed in seven patients. Three of 30 patients with cytokine refractory renal cell carcinoma (RCC; relative risk [RR] 10 %; 95% confidence interval [CI], 0.82-22%) had a partial response. Of the remaining 27 patients with RCC, 4 patients had a minor response, and 10 patients had stable disease lasting a median of 6.4 (range, 4-12) months. The remaining 5 responses occurred in 40 patients (RR, 12.5%; 95% CI, 4.2-26.8%): 2 patients with 5-FU refractory colon carcinoma, 1 patient with hepatoma, 1 patient with paclitaxel-cisplatin-resistant ovarian carcinoma, and 1 patient with cisplatin-resistant head and neck squamous cell carcinoma had a partial response. CONCLUSIONS: For Phase II development, gemcitabine 450-600 mg/m(2) on Days 1, 8, and 15 can be safely combined with 5-FU 200 mg/m(2) given as a continuous infusion (Days 1-21) of a 28-day cycle or gemcitabine 1800 mg/m(2) Days 1 and 8 given with 5-FU 200 mg/m(2) as a continuous infusion (Days 1-14) of a 21-day cycle. The observed antitumor activity in several solid tumors, especially in renal cell carcinoma, warrants broad Phase II evaluation.

Adult↗
PubMed2001

Phase II study of docetaxel, estramustine, and low-dose hydrocortisone in men with hormone-refractory prostate cancer: a final report of CALGB 9780. Cancer and Leukemia Group B.

PURPOSE: To investigate the combination of docetaxel, estramustine (EM), and low-dose hydrocortisone in men with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: Combinations of EM with other antimitotic agents such as docetaxel are synergistic in vitro and show significant clinical activity in patients with HRPC. We studied intravenous administration of docetaxel 70 mg/m(2), oral estramustine, and low-dose daily hydrocortisone in men with HRPC who demonstrated progression after initial hormone therapy. RESULTS: Of the 47 men enrolled onto this multicenter cooperative group study, 46 were assessable for response and/or toxicity. In the 24 patients with measurable disease, there were three complete and nine partial responses for a measurable disease response rate of 50% (12 of 24 patients; 95% confidence interval [CI], 27% to 73%). In the 44 patients in whom pretreatment prostate-specific antigen (PSA) was elevated, 30 (68%) had a 50% or greater decrease, and 25 (57%) had a 75% or greater decrease in PSA. The combined measurable disease and biochemical response rate in all 46 assessable patients was 54% (three complete responses, 22 partial responses, 95% CI, 37% to 71%). The predominant toxicity was neutropenia, with 26% of patients having grade 3 and 30% having grade 4 granulocytopenia; there were no episodes of febrile neutropenia. Other common but mild adverse effects included malaise/fatigue, peripheral edema, and hyperglycemia. The incidence of thromboembolic events during therapy was 9%. With a median follow-up of 17 months, the median survival was 20 months. The median time to disease progression was 8 months for all patients, and 10 months for those with measurable disease. CONCLUSION: This therapy is efficacious and moderately well tolerated in HRPC and should be compared in a phase III trial with mitoxantrone and prednisone.

Aged↗
PubMed2001

Phase I clinical and pharmacogenetic study of weekly TAS-103 in patients with advanced cancer.

PURPOSE: TAS-103 is an inhibitor of both topoisomerase I and II enzymes with broad antitumor activity. It is metabolized to TAS-103-glucuronide (TAS-103-G) predominantly by uridine diphosphate glucuronosyltransferase isoform 1A1 (UGT1A1). We conducted a phase I study to determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of TAS-103 when administered on a weekly schedule to patients with advanced cancer. In addition, we evaluated the influence of UGT1A1 genotype on the pharmacokinetics and toxicity of TAS-103. PATIENTS AND METHODS: Thirty-two patients were treated with escalating doses (50 to 200 mg/m(2)) of TAS-103, administered intravenously over 1 hour each week for 3 weeks. Pharmacokinetic analysis was performed at the 130-, 160-, and 200-mg/m(2) dose levels. UGT1A1 genotypes were determined using reverse-transcription polymerase chain reaction techniques. RESULTS: DLT (grade 3 neutropenia) was observed in 5 of 12 patients at 160 mg/m(2) and in 3 of 6 patients at 200 mg/m(2). At 160 mg/m(2), there was a significant correlation between areas under the curve (AUCs) for TAS-103 and TAS-103-G (r = 0.76, P <.05) and an apparent relationship between TAS-103 AUC and D 15 absolute neutrophil count (r = -0.63, P <.05, n = 11, one outlier excluded). UGT1A1 genotype did not influence clearance of TAS-103. CONCLUSION: We recommend a dose of 130 to 160 mg/m(2), or 250 to 300 mg administered using the above weekly schedule for phase II studies. Further studies to characterize the pharmacodynamics and pharmacogenetics of TAS-103 are warranted.

Adult↗
PubMed2001

Vascular endothelial growth factor and basic fibroblast growth factor urine levels as predictors of outcome in hormone-refractory prostate cancer patients: a cancer and leukemia group B study.

Better prognostic markers are needed for hormone-refractory prostate cancer (HRPC) patients. No single biochemical or clinical parameter can reliably predict patient response to therapy or rapidity of disease progression. Peptide factors involved in major cancer growth pathways, such as tumor angiogenesis, are attractive candidates as markers of low- and high-risk HRPC patients. We analyzed prospectively collected urine specimens from 100 of 390 HRPC patients undergoing therapy with the growth factor antagonist suramin as part of CALGB 9480. Levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were assessed from day 1 of therapy (D1) and day 29 (D29) urine samples from this subset of 100 randomly selected patients. Growth factor levels were determined by standardized ELISA microtiter plate assays from a commercial (bFGF) or proprietary (VEGF) source. Pretreatment urine VEGF levels were predictive of survival. In univariate analysis, patients whose baseline urine VEGF level was < or =28 pg/ml (the median level) had an average survival of 17 months; those with baseline VEGF >28 pg/ml had a significantly shorter survival of 10 months (P = 0.024). This difference corresponded to a 60% increased risk of dying for the higher urine VEGF patients (hazard ratio, 1.62; P = 0.03) and remained significant in multivariate analysis (hazard ratio, 1.72, P = 0.02). No significant correlations between urine bFGF level or change in bFGF levels and survival were found. These results support the notion that certain peptide growth factor-mediated, mitogenic pathways are important in HRPC and that their levels can predict outcome.

Aged↗
PubMed2001

Phase I study of ZD9331 on short daily intravenous bolus infusion for 5 days every 3 weeks with fixed dosing recommendations.

PURPOSE: To conduct a phase I study of ZD9331, a potent, nonpolyglutamatable thymidylate synthase inhibitor using a short daily infusion for 5 consecutive days every 21 days. PATIENTS AND METHODS: Patients with refractory cancer or cancer for which no standard therapy was available were treated in escalating doses using an accelerated titration design. Plasma and urine samples were collected at timed intervals in the first cycle for pharmacokinetic analysis. RESULTS: Seventy-four patients were enrolled at 12 dose levels from a starting dose of 0.4 mg/m(2)/d to 16 mg/m(2)/d and 25 mg/d fixed dosing, of which 67 were assessable for toxicity. Maximum-tolerated dose was reached at 16 mg/m(2)/d. Myelosuppression was dose-limiting, consisting of thrombocytopenia associated with neutropenic fever. Body-surface area did not correlate with drug clearance; therefore, fixed daily dosing of 25 mg/d was studied and found to be tolerable, with two of 12 dose-limiting events. Dose-limiting nonhematologic toxicity consisted of grade 3 erythematous maculopapular rash observed in one patient at 12 mg/m(2)/d and one patient at 25 mg/d. Pharmacokinetic analysis showed nonlinearity, with clearance increasing with dose. The mean clearance and terminal half-life of the drug were 6.6 +/- 2.0 mL/min and 71.3 +/- 27.0 hours, respectively. Area-under-the concentration-time curve was a better predictor of toxicity than dose, using multiple linear regression analyses. Minor response (40% shrinkage of tumor) was observed in one patient with colorectal cancer treated at 12 mg/m(2)/d. CONCLUSION: The recommended dose for ZD9331 on this schedule is 25 mg/d. Neutropenia, thrombocytopenia, and rash were dose-limiting, and efficacy studies in colorectal cancer are indicated.

Adult↗
PubMed2001

Nilutamide: possible utility as a second-line hormonal agent.

OBJECTIVES: To study the ability of nilutamide to induce prostate-specific antigen (PSA) responses in patients with hormone-resistant prostate cancer who had been exposed to prior antiandrogen therapy, because resistance to antiandrogens may be mediated by altered binding to a mutated or overexpressed androgen receptor and because an alternative antiandrogen may overcome such resistance. Nilutamide is a little used antiandrogen that has a chemical structure distinct from that of the other two antiandrogens, flutamide and bicalutamide. METHODS: Fourteen patients with hormone-resistant prostate cancer were treated with nilutamide 150 mg/day (n = 12) or 300 mg/day (n = 2). Seven had been treated with one prior antiandrogen (all with bicalutamide), five with both bicalutamide and flutamide, and two had received bicalutamide and prior chemotherapy. RESULTS: In a retrospective analysis, 7 (50%) of the 14 patients had a greater than 50% decline in their PSA level, and 4 of the 6 patients with bone pain experienced subjective improvement. The median duration of the PSA response was 11 months (range 2 to 28+) with 2 of the 7 patients still experiencing a PSA response. In addition, 3 patients (20%) had brief and minor PSA responses (less than 50%). CONCLUSIONS: A subset of patients, whose disease progresses with prior antiandrogen therapy, may experience a PSA response to nilutamide. The role of nilutamide in such hormone-resistant patients deserves additional prospective study.

Androgen Antagonists↗
PubMed2001

Docetaxel and exisulind in hormone-refractory prostate cancer.

Single-agent docetaxel has been shown to produce a significant decrease in prostate-specific antigen (PSA) levels among patients with hormone-refractory prostate cancer (HRPC). A recent study also showed that exisulind, a sulfone metabolite of the nonsteroidal anti-inflammatory drug sulindac, lengthens the median PSA doubling time in men who had increasing PSA levels after radical prostatectomy. Furthermore, exisulind has shown significant antineoplastic activity in prostate cancer cell lines in vitro and in nude mouse xenograft models. Because preclinical studies have suggested synergistic interactions between docetaxel and exisulind, a phase I/II clinical trial combining these agents has been initiated in patients with HRPC. The primary objective of this study is to determine PSA response and measurable disease response rate of the combination therapy; secondary objectives include toxicity assessment and determination of time to disease progression, duration of response, and overall survival. Accrual is ongoing.

Aged↗
PubMed2001

High-dose doxorubicin, dexrazoxane, and GM-CSF in malignant mesothelioma: a phase II study-Cancer and Leukemia Group B 9631.

Doxorubicin is the most widely studied agent for the treatment of malignant mesothelioma. In conventional doses, the response rate is approximately 17%. Higher dose doxorubicin has been successfully employed in other tumor types. Dexrazoxane has been demonstrated to reduce the cardiac toxicity associated with long term, chronic use of doxorubicin. Based upon phase I data generated by the Cancer and Leukemia Group B (CALGB) indicating that doxorubicin at a dose of 120 mg/m(2) when combined with dexrazoxane and GM-CSF could be safely administered, the CALGB undertook a phase II study of high-dose doxorubicin in patients with malignant mesothelioma. Toxicity was excessive, necessitating protocol modification and ultimately protocol termination. There were no objective responses observed. We conclude that high-dose doxorubicin administered with dexrazoxane is unacceptably toxic in this patient population.

Adult↗